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粪菌移植、γδT 细胞免疫治疗与帕博利珠单抗在难治性晚期胰腺癌中的协同效应:一例病例报告

英文原题:Synergistic Effect of Fecal Microbiota Transplantation, γδT Cell Immunotherapy, and Pembrolizumab in Refractory Advanced Pancreatic Cancer: A Case Report.

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Synergistic Effect of Fecal Microbiota Transplantation, γδT Cell Immunotherapy, and Pembrolizumab in Refractory Advanced Pancreatic Cancer: A Case Report.

PubMed 2026/01/20(内容时间) J Gastrointest Cancer Q3 · IF 2.2(JCR 2025)

研究概要

本病例提示,FMT联合γδ T细胞治疗可能是晚期PC的一种有前景的免疫治疗策略。需要进一步研究以验证这些发现。

研究思路结论见上方概要

胰腺癌(PC)仍然是最致命的恶性肿瘤之一,治疗选择有限,尤其是在晚期阶段。新兴的免疫治疗策略,如Gamma Delta(γδ)T细胞疗法联合微生物群管理,已显示出前景。病例介绍:我们报告一例75岁男性,诊断为晚期低分化PC,在接受一种新型治疗方法后表现出显著的临床改善,该方案联合了粪菌移植(FMT)、γδ T细胞疗法和pembrolizumab。由于不良反应,初始化疗和放疗被终止。治疗前CA19-9(1206 U/mL)显著升高,肿瘤标志物CEA、CA15-3和CA125均在正常范围内。未发现致病性突变(如BRCA1/2、PALB2)。综合评估显示肿瘤进展、免疫抑制和肠道菌群失调,因此在pembrolizumab的基础上引入了FMT和γδ T细胞疗法。结果:联合治疗导致循环肿瘤细胞(CTC)清除,CA19-9降至72 U/mL,临床症状改善,并且CT证实肿瘤体积显著缩小。耐受性极好,未发生严重不良事件。

展开英文摘要原文

BACKGROUND: Pancreatic cancer (PC) remains one of the most lethal malignancies with limited treatment options, particularly in advanced stages. Emerging immunotherapeutic strategies, such as Gamma Delta (γδ) T cell therapy paired with microbiota management, have demonstrated promise. CASE PRESENTATION: We report a case of a 75-year-old male diagnosed with advanced-stage and poorly differentiated PC who demonstrated significant clinical improvement following a novel therapeutic approach combining fecal microbiota transplantation (FMT), γδ T cell therapy, and pembrolizumab. Initial chemotherapy and radiotherapy were discontinued due to adverse effects. Pre-treatment the CA19-9 (1206 U/mL), tumor markers were significantly elevated with CEA, CA15-3 and CA125 all within normal limits. No pathogenic mutations (e.g., BRCA1/2, PALB2) were identified. A comprehensive assessment revealed tumor progression, immunosuppression, and gut microbiota dysbiosis, resulting in FMT and γδ T cell therapy being introduced alongside pembrolizumab. OUTCOMES: The combination therapy resulted in the clearance of circulating tumor cells (CTCs), normalization of CA19-9 to 72 U/mL, improved clinical symptoms, and a marked reduction in tumor size, as confirmed by CT. Tolerability was excellent with no serious adverse events occurred. CONCLUSION: This case suggests that FMT combined with γδ T cell therapy may be a promising immunotherapeutic strategy for advanced PC. Further studies are needed to validate these findings.

论文信息

作者
Alnaggar M、Chen Y、Wang C、Wang S、Zhu F、Lin Y、Abdu FA、Gong L
第一作者单位
Department of Gastrointestinal Oncology, Modern Hospital Guangzhou, Guangzhou, Guangdong, China. dr.alnaggar@hotmail.com.China
通讯作者单位
Cancer Center, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China. yongshun2007@163.com.China
文献类型
病例报告
期刊
Journal of gastrointestinal cancer2026 Jan 20
原文标识
PubMed 41557025 · DOI 10.1007/s12029-025-01368-9